ABSTRACT
Metastasis is the leading cause of cancer-related deaths. Despite this relevance, there is no specific therapy targeting metastasis. The interaction of the tumor cell with platelets, forming microemboli is crucial for successful hematogenous dissemination. Heparin disrupts it by a P-selectin-mediated event. However, its clinical use for this purpose is hindered by the requirement of high doses, leading to anticoagulant-related side effects. In this study, we obtained a low-anticoagulant heparin through the fractionation of a pharmaceutical bovine heparin. This derivative was referred to as LA-hep and we investigated its efficacy in inhibiting metastases and explored its capacity of suppressing the interaction between tumor cells and platelets. Our data revealed that LA-hep is as efficient as porcine unfractionated heparin in attenuating lung metastases from melanoma and colon adenocarcinoma cells in an assay with a single intravenous administration. It also prevents platelet arrest shortly after cell injection in wild-type mice and suppresses melanoma-platelets interaction in vitro. Moreover, LA-hep blocks P-selectin's direct binding to tumor cells and platelet aggregation, providing further evidence for the role of P-selectin as a molecular target. Even in P-selectin-depleted mice which developed a reduced number of metastatic foci, both porcine heparin and LA-hep further inhibited metastasis burden. This suggests evidence of an additional mechanism of antimetastatic action. Therefore, our results indicate a dissociation between the heparin anticoagulant and antimetastatic effects. Considering the simple and highly reproducible methodology used to purify LA-hep along with the data presented here, LA-hep emerges as a promising drug for future use in preventing metastasis in cancer patients.
Subject(s)
Adenocarcinoma , Colonic Neoplasms , Melanoma , Humans , Animals , Cattle , Mice , Heparin/pharmacology , Anticoagulants/pharmacology , P-Selectin/metabolism , Melanoma/pathology , Adenocarcinoma/pathology , Colonic Neoplasms/pathology , Blood Platelets/metabolism , Pharmaceutical Preparations/metabolism , Neoplasm Metastasis/pathologyABSTRACT
BACKGROUND: Social cognition (SC) impairments contribute to the dependence of people with Alzheimer disease (AD), influencing their functional disability and the burden on family members and caregivers. Our objective was to longitudinally investigate the relationship between SC and cognitive and clinical variables in persons with AD and their caregivers. We also evaluated the different SC predictors from 3 perspectives: people with AD, caregivers of people with AD, and discrepancy analysis. METHODS: In all, 137 dyads (people with AD and their caregivers) underwent 2 assessments: at baseline (M1) and after 1 year (M2). During follow-up, 58 dyads were excluded, and the study was thus concluded with 79. RESULTS: Longitudinal analysis of the people with AD showed that while some cognitive functions declined (which is consistent with disease progression), SC impairments showed a more stable pattern. Another interesting result was related to SC predictors. For people with AD, SC was associated with cognition at both time points. For caregivers, besides cognition, other predictors included reduced functional abilities and quality of life in people with AD. These results are consistent with the discrepancy predictors. CONCLUSION: The stable pattern in SC functioning over 12 months in AD suggests that this neurocognitive domain may be influenced more by emotional processing than by cognitive impairment. In addition, the SC predictors showed that the investigation of different points of view enables a more global understanding, contributing to better and more targeted treatment for the patient.
Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/psychology , Quality of Life/psychology , Brazil , Social Cognition , Cognition , Caregivers/psychologyABSTRACT
The COVID-19 pandemic has raised significant concerns about the management and care for people with dementia and their caregivers. In this context, this work will discuss how social isolation or social distancing caused by the pandemic may impact the clinical management of people with dementia, caregivers' health, and dementia research. The pandemic disrupts all forms of social interaction and may increase the behavioral impairment of people with dementia. Regarding pharmacological treatment, telemedicine is an option, but the context of social isolation raises questions about how to manage people with dementia with lack of cognitive stimulation and non-pharmacological treatment. In addition, the impact of the pandemic on caregivers should be considered. There is some evidence that telephone counseling can reduce depressive symptoms of caregivers of people with dementia. In dementia research, social isolation imposes researchers to modify their study protocols in order to continue collecting data by developing remote tools to assess the participants such as electronic informed consent and online questionnaires and tests. Thus, there is an urgent need for the evaluation and refinement of interventions to address several cognitive, behavioral, and clinical aspects of the long-term impact of the pandemic in dementia.
A pandemia causada pelo COVID-19 desencadeia grandes preocupações sobre o manejo e cuidados com as pessoas com demência e seus cuidadores. Neste contexto, discutiremos como o isolamento social causado pela pandemia pode impactar o manejo clínico de pessoas com demência, a saúde do cuidador e a pesquisa sobre demência. A pandemia interrompe todas as formas de interação social e pode causar aumento do comprometimento dos sintomas neuropsiquiátricos nas pessoas com demência. Em relação ao tratamento farmacológico, a telemedicina é uma opção, mas o contexto de isolamento social levanta questões sobre como manejar as pessoas com demência com falta de estimulação cognitiva ou intervenções nãofarmacológicas. Além disso, o impacto da pandemia sobre os cuidadores deve ser considerado. Existem evidências de que o aconselhamento telefônico pode reduzir os sintomas depressivos dos cuidadores. Além disso, o isolamento social impõe que pesquisadores modifiquem seus protocolos de pesquisa com o objetivo de continuar coletando dados, através do desenvolvimento de ferramentas remotas para avaliar os participantes, como o consentimento livre e esclarecido eletrônico e questionários e testes online. Assim, há uma necessidade urgente de avaliação e refinamento das intervenções para abordar aspectos cognitivos, comportamentais e clínicos do impacto de longo prazo da pandemia na demência.
ABSTRACT
ABSTRACT. The COVID-19 pandemic has raised significant concerns about the management and care for people with dementia and their caregivers. In this context, this work will discuss how social isolation or social distancing caused by the pandemic may impact the clinical management of people with dementia, caregivers' health, and dementia research. The pandemic disrupts all forms of social interaction and may increase the behavioral impairment of people with dementia. Regarding pharmacological treatment, telemedicine is an option, but the context of social isolation raises questions about how to manage people with dementia with lack of cognitive stimulation and non-pharmacological treatment. In addition, the impact of the pandemic on caregivers should be considered. There is some evidence that telephone counseling can reduce depressive symptoms of caregivers of people with dementia. In dementia research, social isolation imposes researchers to modify their study protocols in order to continue collecting data by developing remote tools to assess the participants such as electronic informed consent and online questionnaires and tests. Thus, there is an urgent need for the evaluation and refinement of interventions to address several cognitive, behavioral, and clinical aspects of the long-term impact of the pandemic in dementia.
RESUMO. A pandemia causada pelo COVID-19 desencadeia grandes preocupações sobre o manejo e cuidados com as pessoas com demência e seus cuidadores. Neste contexto, discutiremos como o isolamento social causado pela pandemia pode impactar o manejo clínico de pessoas com demência, a saúde do cuidador e a pesquisa sobre demência. A pandemia interrompe todas as formas de interação social e pode causar aumento do comprometimento dos sintomas neuropsiquiátricos nas pessoas com demência. Em relação ao tratamento farmacológico, a telemedicina é uma opção, mas o contexto de isolamento social levanta questões sobre como manejar as pessoas com demência com falta de estimulação cognitiva ou intervenções nãofarmacológicas. Além disso, o impacto da pandemia sobre os cuidadores deve ser considerado. Existem evidências de que o aconselhamento telefônico pode reduzir os sintomas depressivos dos cuidadores. Além disso, o isolamento social impõe que pesquisadores modifiquem seus protocolos de pesquisa com o objetivo de continuar coletando dados, através do desenvolvimento de ferramentas remotas para avaliar os participantes, como o consentimento livre e esclarecido eletrônico e questionários e testes online. Assim, há uma necessidade urgente de avaliação e refinamento das intervenções para abordar aspectos cognitivos, comportamentais e clínicos do impacto de longo prazo da pandemia na demência.
Subject(s)
Humans , Behavioral Symptoms , Caregivers , Coronavirus Infections , DementiaABSTRACT
Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system. OBJECTIVE: Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD). METHODS: This systematic review followed PRISMA methodology. A search of Pubmed, Scopus and Web of Science electronic databases was carried out in September, 2018, identifying experimental investigations of metamemory and dementia. RESULTS: We included 21 studies. The most common tasks used were judgement of learning, feeling of knowing, judgement of confidence and global prediction. The rates of discrepancy between PwAD and caregivers still need further research. The Rey Auditory Verbal Learning Test was the most used list of words. PwAD are able to accurately rate their memory functioning and performance, when the evaluation is done soon afterwards. PwAD tend to overestimate their functioning and performance when the judgement involves forward-looking vision. CONCLUSION: In the context of metamemory impairment, clinicians and caregivers should seek interventions aiming to identify compensatory styles of functioning. This systematic review provides initial evidence for the use of metamemory measures as part of broader assessments evaluating Alzheimer's disease.
Metamemoria é a consciência do próprio conhecimento e controle da memória, e refere-se à capacidade online de reunir informações sobre o estado atual do sistema de memória. OBJETIVO: Metamemória é a consciência sobre o próprio conhecimento e controle da memória. Nós conduzimos uma revisão sistemática para identificar os tipos de tarefa usadas para avaliar o monitoramento da metamemória, os estímulos usados nessas tarefas, suas limitações e resultados em pessoas com doenças de Alzheimer. MÉTODOS: Esta revisão sistemática usou a metodologia PRISMA. Uma busca nas bases Pubmed, Scopus e Web of Science foi feita em Setembro de 2018. Foram identificados estudos experimentais em metamória e demência. RESULTADOS: Foram incluídos 21 estudos que se enquadravam nos critérios de inclusão. As tarefas mais comuns foram "judgement of learning", "feeling of knowing", "judgement of confidence" and "global prediction". As discrepâncias, em termos de monitoramento de metamemória, ainda necessitam de pesquisas futuras. O Rey Auditory Verbal Learning Test foi a lista de palavras mais usada. Pessoas com doença de Alzheimer são capazes de avaliar de forma acurada o seu funcionamento da memória, quando a avaliação é feita em um momento posterior. Eles tendem a superestimar seu funcionamento quando o julgamento é feito em uma visão de futuro. CONCLUSÃO: No contexto do comprometimento da metamemória, é necessário que clínicos e cuidadores procurem intervenções com o objetivo de identificar estilos compensatórios de funcionamento. Assim, esta revisão sistemática fornece evidências iniciais sobre o uso de medidas de metamemória como parte de avaliações mais amplas na doença de Alzheimer.
ABSTRACT
ABSTRACT Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system. Objective: Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD). Methods: This systematic review followed PRISMA methodology. A search of Pubmed, Scopus and Web of Science electronic databases was carried out in September, 2018, identifying experimental investigations of metamemory and dementia. Results: We included 21 studies. The most common tasks used were judgement of learning, feeling of knowing, judgement of confidence and global prediction. The rates of discrepancy between PwAD and caregivers still need further research. The Rey Auditory Verbal Learning Test was the most used list of words. PwAD are able to accurately rate their memory functioning and performance, when the evaluation is done soon afterwards. PwAD tend to overestimate their functioning and performance when the judgement involves forward-looking vision. Conclusion: In the context of metamemory impairment, clinicians and caregivers should seek interventions aiming to identify compensatory styles of functioning. This systematic review provides initial evidence for the use of metamemory measures as part of broader assessments evaluating Alzheimer's disease.
RESUMO Metamemoria é a consciência do próprio conhecimento e controle da memória, e refere-se à capacidade online de reunir informações sobre o estado atual do sistema de memória. Objetivo: Metamemória é a consciência sobre o próprio conhecimento e controle da memória. Nós conduzimos uma revisão sistemática para identificar os tipos de tarefa usadas para avaliar o monitoramento da metamemória, os estímulos usados nessas tarefas, suas limitações e resultados em pessoas com doenças de Alzheimer. Métodos: Esta revisão sistemática usou a metodologia PRISMA. Uma busca nas bases Pubmed, Scopus e Web of Science foi feita em Setembro de 2018. Foram identificados estudos experimentais em metamória e demência. Resultados: Foram incluídos 21 estudos que se enquadravam nos critérios de inclusão. As tarefas mais comuns foram "judgement of learning", "feeling of knowing", "judgement of confidence" and "global prediction". As discrepâncias, em termos de monitoramento de metamemória, ainda necessitam de pesquisas futuras. O Rey Auditory Verbal Learning Test foi a lista de palavras mais usada. Pessoas com doença de Alzheimer são capazes de avaliar de forma acurada o seu funcionamento da memória, quando a avaliação é feita em um momento posterior. Eles tendem a superestimar seu funcionamento quando o julgamento é feito em uma visão de futuro. Conclusão: No contexto do comprometimento da metamemória, é necessário que clínicos e cuidadores procurem intervenções com o objetivo de identificar estilos compensatórios de funcionamento. Assim, esta revisão sistemática fornece evidências iniciais sobre o uso de medidas de metamemória como parte de avaliações mais amplas na doença de Alzheimer.
